PIK3CD and Down syndrome: Activated PI3Kδ syndrome (APDS) is an IEI (3), thus far comprising APDS1, caused by gain of function (GOF) mutations in PIK3CD coding for the catalytic p101δ subunit (4, 5); APDS2 with loss of function (LOF) variants in the regulatory PIK3R1 coding for the regulatory p85α subunit (4) and LOF mutations in phosphatase and tensin homolog (PTEN) (APDS-L) (5).